This clinical trial is evaluating a drug called ART0380 in participants with advanced or metastatic solid tumors. The main goals of this study are to: * Find the recommended dose of ART0380 that can be given safely to participants alone and in combination with gemcitabine or irinotecan * Learn more about the side effects of ART0380 alone and in combination with gemcitabine or irinotecan * Learn more about the effectiveness of ART0380 alone and in combination with gemcitabine or irinotecan
ART0380 is a new investigational medicinal product that is a potent and selective inhibitor of Ataxia telangiectasia and Rad3-related (ATR). ART0380 is being developed as an oral anti-cancer agent for the treatment of participants with cancers that harbor defects in deoxyribonucleic acid (DNA) repair and in combination with agents including those that cause DNA damage. This study is an open-label Phase I/IIa study designed to evaluate the safety, tolerability, PK and preliminary efficacy of ART0380 as monotherapy or in combination with gemcitabine or irinotecan in participants with advanced or metastatic solid tumors, advanced or solid tumors that fail to express Ataxia-Telangiectasia Mutated protein kinase (ATM) by immunohistochemistry, and high grade serous ovarian, primary peritoneal or fallopian tube carcinoma.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
502
Participants will receive ART0380 by mouth either intermittently (either once daily 3 days on, 4 days off; days 2-4 and 9-11;or days 1-3 and 8-10) or continuously (once daily each day) in 21 day cycles.
Gemcitabine was administered on Days 1 and 8 of a 21-day cycle.
Irinotecan will be administered as a 90-minute infusion on Days 1 and 8 of a 21 day cycle.
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGMayo Clinic (Arizona)
Scottsdale, Arizona, United States
RECRUITINGUniversity of Arkansas - Winthrop P. Rockefeller Cancer Institute
Little Rock, Arkansas, United States
RECRUITINGUSC Norris Comprehensive Cancer Center
Los Angeles, California, United States
Part A: Maximum tolerated dose (MTD) by the number of participants with dose limiting toxicities (DLTs) from ART0380 monotherapy and in combination with gemcitabine or irinotecan
Time frame: From Cycle 0 Day -2 to Cycle 1 Day 21. Each cycle is 21 days.
Parts B1/B3/B4: Number of participants with adverse events following administration of ART0380 monotherapy and/or in combination with irinotecan at RP2Ds.
Safety reported as incidence of adverse events
Time frame: From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380. Each cycle is 21 days.
Part B2: Progression free survival by RECIST 1.1 in participants receiving ART0380 in combination with gemcitabine or gemcitabine alone
Progression free survival (PFS)
Time frame: Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Parts B5/B6/B7: Object Response Rate (ORR) based on RECIST 1.1 to access anti-tumor activity of ART0380 in combination with irinotecan in each cohort.
Objective Response Rate (ORR)
Time frame: Every 6 weeks from Cycle 1 Day 1, until disease progression or death or start of a new anti-cancer therapy, up to 2 years. Each Cycle is 21 days.
Part B2: Number of participants with adverse events following administration of ART0380 in combination with gemcitabine or gemcitabine alone
Time frame: From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or gemcitabine. Each cycle is 21 days.
Part B5/B6/B7: Number of participants with adverse events following administration of ART0380 at the RP2D in combination with irinotecan.
Time frame: From Cycle 1 Day 1 until up to 30 days after the last dose of ART0380 or irinotecan. Each cycle is 21 days.
Pharmacokinetic Analysis (single dose): determine the plasma concentration of ART0380 when given alone and in combination
Time frame: PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Pharmacokinetic Analysis (multiple dose): determine the plasma concentration of ART0380 when given alone and in combination
Time frame: PK will be measured at each cycle from Cycle 0 to Cycle 4. Each cycle is 21 days.
Pharmacokinetic Analysis: Renal clearance of ART0380
Time frame: Urine PK will be measured during Cycle 1. Cycle 1 is 21 days.
Parts A1, A2, A3, B1, B3, B4: Objective response rate based on RECIST 1.1
Time frame: Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Parts A1, A2, A3, B1, B3, B4, B5, B6, and B7: Duration of response based on RECIST 1.1
Time frame: Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Parts A1, A2, A3, B1, B3, B4, B5, B6, and B7: Progression free survival based on RECIST 1.1
Time frame: Every 6 weeks from Cycle 1 Day 1 for 18 weeks, then every 9 weeks up to approximately 24 months. Each cycle is 21 days.
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve from zero to 12 hours (AUC0-12)
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Maximum plasma Concentration (Cmax) in a fasting and fed state.
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Time to Maximum plasma concentration (Tmax) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve from zero to the time of last plasma concentration (AUC0-t) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Terminal half-life (t1/2) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-tau)) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area Under The Curve Plasma Concentration Time Curve over the last 12-h dosing interval (AUC012) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve over the dosing interval (AUC(0-infinity)) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve for Oral Clearance (CL/F) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Pharmacokinetic Analysis: Area under the concentration-time curve for Volume of Distribution (Vz/F) in a fasting and fed state
Time frame: PK will be measured during Cycle 1. Cycle 1 is 21 days
Parts B1/B3/B4/B5/B6/B7: Response and disease progression by Serological tumor markers (CA-19-9, CAE, CA-125, and Prostate Specific Antigen (PSA)).
Time frame: Tumor markers will be measured for 18 weeks, then every 9 weeks thereafter.
Parts B1/B3/B4/B5/B6/B7: Overall Survival
Time frame: After first dose through PFS/OS follow-up.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Sansum Clinic
Santa Barbara, California, United States
RECRUITINGProvidence Medical Foundation
Santa Rosa, California, United States
RECRUITINGRocky Mountain Cancer Center
Denver, Colorado, United States
RECRUITINGSarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGFlorida Cancer Specialists
Fort Myers, Florida, United States
RECRUITINGMayo Clinic (Florida)
Jacksonville, Florida, United States
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